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1.
Einstein (Säo Paulo) ; 20: eAO6450, 2022. tab, graf
Article in English | LILACS | ID: biblio-1364794

ABSTRACT

ABSTRACT Objective To understand the feasibility of FGFR3 tests in the Brazilian public health context, and to sample the mutational burden of this receptor in high-grade muscle invasive bladder cancer. Methods A total of 31 patients with high-grade muscle-invasive bladder cancer were included in the present study. Either transurethral resection of bladder tumor or radical cystectomy specimens were analyzed. Formalin-fixed paraffin-embedded tissue blocks were sectioned, hematoxylin and eosin stained, and histologic sections were reviewed. Total RNA was extracted using the RNeasy DSP formalin-fixed paraffin-embedded kit. Qualitative results were displayed in Rotor-Gene AssayManager software. Results Six patients were excluded. From the samples analyzed, four (16.7%) were considered inadequate and could not have their RNA extracted. Two patients presented FGFR3 mutations, accounting for 9.5% of material available for adequate analysis. The two mutations detected included a Y373C mutation in a male patient and a S249C mutation in a female patient. Conclusion FGFR3 mutations could be analyzed in 84% of our cohort and occurred in 9.5% of patients with high-grade muscle invasive bladder cancer in this Brazilian population. FGFR3 gene mutations are targets for therapeutic drugs in muscle-invasive bladder cancer. For this reason, know the frequency of these mutations can have a significant impact on public health policies and costs provisioning.


Subject(s)
Urinary Bladder Neoplasms/genetics , Carcinoma, Transitional Cell/genetics , Carcinoma, Transitional Cell/metabolism , Carcinoma, Transitional Cell/pathology , Receptor, Fibroblast Growth Factor, Type 3/genetics , Receptor, Fibroblast Growth Factor, Type 3/metabolism , Brazil , RNA , Prevalence , Eosine Yellowish-(YS) , Hematoxylin , Muscles/metabolism , Muscles/pathology , Mutation
2.
Rev. Assoc. Med. Bras. (1992) ; 67(1): 64-70, Jan. 2021. tab, graf
Article in English | LILACS | ID: biblio-1287776

ABSTRACT

SUMMARY OBJECTIVE: Bladder cancer under the age of 40 is extremely rare. Bladder cancer development involves complex and multi-stage processes, one of which is the DNA damage repair mechanism. In this retrospective study, we aimed to evaluate the histopathological features of bladder urothelial carcinoma seen in patients under 40 years of age and tumor microsatellite instability status using immunohistochemistry. METHODS: A total of 50 patients under the age of 40 with urothelial bladder carcinoma from two different centers in the same country were included. Expression of the mismatch repair proteins MLH1, MSH2, MSH6, and PMS2 was analyzed by immunohistochemistry. RESULTS: Age at the time of diagnosis ranged from 17 to 40 years old. Most tumors were non-invasive papillary urothelial carcinoma. Two cases had nuclear loss of MSH-6 and PMS-2. We observed that tumor grade, tumor stage, presence of tumor differentiation, and infiltrative growth pattern of the tumor have significant impact on prognosis, but microsatellite instability does not have an effective role in bladder carcinogenesis in young patients. CONCLUSIONS: Our results indicate that the presence of microsatellite instability is not related to the low tumor grade and stage in urothelial neoplasms in young patients, suggesting that urothelial carcinoma of the bladder in young patients may represent a genetically stable form of neoplasia.


Subject(s)
Humans , Adolescent , Adult , Young Adult , Carcinoma, Transitional Cell/genetics , Microsatellite Instability , Urinary Bladder/metabolism , Retrospective Studies , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , DNA Mismatch Repair
3.
Chinese Journal of Oncology ; (12): 1001-1006, 2021.
Article in Chinese | WPRIM | ID: wpr-920981

ABSTRACT

Human epidermal growth factor receptor 2 (HER-2) plays an important role in carcinogenesis and development of urothelial carcinoma. Overexpression of HER-2 is associated with poor prognosis of urothelial carcinoma. Although there is no significant benefit from anti-HER-2 targeted therapies of monoclonal antibody and tyrosine kinase inhibitor, Anti-HER-2 antibody-drug conjugate (HER-2-ADC) has shown a promising efficacy in urothelial carcinoma patients with HER-2 overexpression. Therefore, effectively screening the potential beneficiaries of HER-2-ADC drugs has become a new challenge. However, standardized HER-2 scoring system for urothelial carcinoma has yet to be developed. Thus, the Committees organized experts to reach this expert consensus based on the clinical practice of HER-2 expression, gene amplification and mutation testing in urothelial carcinoma, combined with the current research progress and internal discussion of committee members, in order to construct HER-2 testing standard of urothelial carcinoma and improve the accuracy of interpretation, to guide the clinical application.


Subject(s)
Carcinoma, Transitional Cell/genetics , Consensus , Humans , Receptor, ErbB-2/genetics , Urinary Bladder Neoplasms/genetics
4.
Int. braz. j. urol ; 43(2): 224-229, Mar.-Apr. 2017. tab, graf
Article in English | LILACS | ID: biblio-840826

ABSTRACT

ABSTRACT Introduction Recently, expression of the UHRF1 gene was found to be up-regulated in numerous neoplasms, including the urinary bladder transitional cell carcinoma (TCC). Objective The aim of our study was to determine if the expression levels of UHRF1 gene correlates with the major pathological characteristics of the tumor and patients’ clinical outcome. Materials and Methods In our study, we have analyzed the tissue samples derived from group of 70 patients with histologically confirmed TCC of the urinary bladder, while normal urinary bladder mucosa obtained from 40 patients with nonmalignant diseases was used as a negative control group. Expression of UHRF1 gene in each patient sample was determined using reverse transcriptase-polymerase chain reaction. Results UHRF1 gene expression was found to be app. 2.5 times higher in samples from patients with TCC in comparison with normal epithelium derived from control group patients. Analysis show that gene expression correlates with the malignancy of the tumor. A highly significant differences were found between the expression values of samples from low and high grade TCC, as well as between the high grade and control group. UHRF1 expression was higher in patients with non-muscle invasive disease than in those with muscle invasive disease. Conclusions The result of this study indicates that UHRF1 gene expression levels correlates with the major pathological characteristics of TCC samples and with the clinical outcome of those patients. Determination of UHRF1 gene expression could have a potential to be used as a sensitive molecular marker in patients with urinary bladder cancer.


Subject(s)
Humans , Male , Female , Adult , Aged , Aged, 80 and over , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Carcinoma, Transitional Cell/genetics , Carcinoma, Transitional Cell/pathology , Gene Expression Regulation, Neoplastic , CCAAT-Enhancer-Binding Proteins/analysis , CCAAT-Enhancer-Binding Proteins/genetics , Reference Values , Urinary Bladder/pathology , Genetic Markers , Statistics, Nonparametric , Reverse Transcriptase Polymerase Chain Reaction , Ubiquitin-Protein Ligases , Tumor Burden , Neoplasm Grading , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging
5.
Yonsei Medical Journal ; : 865-871, 2016.
Article in English | WPRIM | ID: wpr-63339

ABSTRACT

PURPOSE: Our previous high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry study identified bladder cancer (BCA)-specific urine metabolites, including carnitine, acylcarnitines, and melatonin. The objective of the current study was to determine which metabolic pathways are perturbed in BCA, based on our previously identified urinary metabolome. MATERIALS AND METHODS: A total of 135 primary BCA samples and 26 control tissue samples from healthy volunteers were analyzed. The association between specific urinary metabolites and their related encoding genes was analyzed. RESULTS: Significant alterations in the carnitine-acylcarnitine and tryptophan metabolic pathways were detected in urine specimens from BCA patients compared to those of healthy controls. The expression of eight genes involved in the carnitine-acylcarnitine metabolic pathway (CPT1A, CPT1B, CPT1C, CPT2, SLC25A20, and CRAT) or tryptophan metabolism (TPH1 and IDO1) was assessed by RT-PCR in our BCA cohort (n=135). CPT1B, CPT1C, SLC25A20, CRAT, TPH1, and IOD1 were significantly downregulated in tumor tissues compared to normal bladder tissues (p<0.05 all) of patients with non-muscle invasive BCA, whereas CPT1B, CPT1C, CRAT, and TPH1 were downregulated in those with muscle invasive BCA (p<0.05), with no changes in IDO1 expression. CONCLUSION: Alterations in the expression of genes associated with the carnitine-acylcarnitine and tryptophan metabolic pathways, which were the most perturbed pathways in BCA, were determined.


Subject(s)
Aged , Biomarkers/metabolism , Carcinoma, Transitional Cell/genetics , Carnitine/analogs & derivatives , Case-Control Studies , Female , Humans , Male , Metabolic Networks and Pathways/physiology , Middle Aged , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Urinary Bladder Neoplasms/genetics
6.
Article in English | WPRIM | ID: wpr-148912

ABSTRACT

PURPOSE: To compare the expression of survivin and its association with clinicopathological criteria in major types of urinary bladder carcinoma, specifically, transitional cell carcinoma with and without squamous differentiation and squamous cell carcinoma. MATERIALS AND METHODS: Immunohistochemical staining for survivin and Ki67 was performed on paraffin-embedded sections of 104 carcinomas: 52 transitional cell carcinoma, 20 transitional cell carcinoma with squamous differentiation, and 32 squamous cell carcinoma. Expression of survivin in >10% of tumor cells was described as altered survivin status. Ki67 staining in >20% of tumor cells was described as a high proliferation index. RESULTS: Altered survivin expression was detected in 60/104 specimens (58%) and was significantly more frequent in transitional cell carcinoma (78%) than in squamous cell carcinoma (38%) or transitional cell carcinoma with squamous differentiation (40%) (p<0.0001). In transitional cell carcinoma but not in squamous cell carcinoma, altered survivin status was associated with higher tumor grade, higher proliferation index, and recurrence. In the whole specimens, altered survivin expression was significantly associated with advanced stage (p<0.001), recurrence (p=0.005), distant metastasis (p<0.001), and death (p=0.001). In the multivariate analysis, altered survivin was an independent poor prognostic factor for recurrence. CONCLUSIONS: Unlike in transitional cell carcinoma, alteration of survivin expression in squamous cell carcinoma occurs less frequently and is not associated with features of tumor aggression or patient outcome. These findings raise a question: are urinary bladder carcinoma patients with squamous cell carcinoma type suitable candidates for survivin vaccine? This is an important question to be answered before approving the vaccine in management.


Subject(s)
Carcinoma, Squamous Cell/genetics , Carcinoma, Transitional Cell/genetics , Female , Humans , Inhibitor of Apoptosis Proteins/genetics , Ki-67 Antigen/metabolism , Male , Middle Aged , Multivariate Analysis , Neoplasm Grading , Neoplasm Metastasis , Neoplasm Recurrence, Local , Neoplasm Staging , Prognosis , Treatment Outcome , Biomarkers, Tumor , Urinary Bladder/pathology , Urinary Bladder Neoplasms/genetics
7.
Int. braz. j. urol ; 39(1): 95-102, January-February/2013. tab, graf
Article in English | LILACS | ID: lil-670368

ABSTRACT

Purpose Bladder cancer (BC) is the second most common malignancy of the urinary tract, with high mortality. The knowledge of the molecular pathways associated with BC carcinogenesis is crucial to identify new diagnostic and prognostic biomarkers. MicroRNAs (miRNAs) are short non-coding RNA molecules that play important roles in the regulation of gene expression by acting directly on mRNAs. miR-145 has been considered as a tumor suppressor, which targets the c-MYC, MUC-1 and FSCN1 genes. Our aim was to evaluate the expression profile of miR-145 in low-grade non-invasive and high-grade invasive bladder urothelial carcinomas. Materials and Methods We studied 30 specimens of low-grade, non-invasive pTa and 30 of pT2/pT3 high-grade invasive UC obtained by transurethral resection or radical cystectomy, followed over a mean time of 16.1 months. Normal controls were represented by five samples of normal bladder biopsy from patients who underwent retropubic prostatectomy to treat BPH. miRNA extraction and cDNA generation were performed using commercial kits. Analysis was performed by qRT-PCR, and miR-145 expression was calculated using the 2-∆∆ct method; we used RNU-43 and RNU-48 as endogenous controls. Results miR-145 was under-expressed in 73.3% and 86.7% of pTa and pT2/pT3, respectively, with expression means of 1.61 for the former and 0.66 for the last. There were no significant differences in miR-145 expression and histological grade, tumor stage, angiolymphatic neoplastic invasion and tumor recurrence. Conclusion miR-145 is under-expressed in low-grade, non-invasive and high-grade invasive urothelial bladder carcinoma and may play an important role in the carcinogenesis pathway, being an interesting candidate diagnostic marker. .


Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Carcinoma, Transitional Cell/genetics , MicroRNAs/analysis , Urinary Bladder Neoplasms/genetics , Analysis of Variance , Carcinogens/metabolism , Carcinoma, Transitional Cell/metabolism , Gene Expression , Neoplasm Grading , Neoplasm Recurrence, Local , Statistics, Nonparametric , Biomarkers, Tumor/analysis , Urinary Bladder Neoplasms/metabolism
8.
LJM-Libyan Journal of Medicine. 2009; 4 (4): 143-145
in English | IMEMR | ID: emr-146578

ABSTRACT

The expression of EGFR and p53 has not been adequately studied as a prognostic tool in urinary bladder tumors. We analyzed 74 bladder cancer samples from Egypt for EGFR and p53 expression using immunohistochemistry. The tumors were of different histological types, grades and clinical stages, and with established lymph node status. Almost 61% of the tumors showed positive membranous EGFR expression and 74.3% had positive nuclear staining of p53. Analysis of correlation of the IHC staining with clinical variables showed a significant correlation only between EGFR expression and histological type [p=0.002, ANOVA], in that the expression was higher in squamous cell carcinomas than in other histological types. There were no significant correlations between p53 or EGFR with the other clinicopathological variables, including age, sex, staging, grading, and lymph node status. Further studies are needed to determine if EGFR and p53 might be used as prognostic tools in bladder cancer


Subject(s)
Humans , Male , Female , Urinary Bladder Neoplasms/genetics , Carcinoma, Squamous Cell/genetics , Carcinoma, Transitional Cell/genetics , Immunohistochemistry , ErbB Receptors , Gene Expression Regulation, Neoplastic , Analysis of Variance , Chi-Square Distribution
9.
Article in English | WPRIM | ID: wpr-37035

ABSTRACT

The oncogenic isoform of the p63 protein, delta NP63, plays an important role in the pathogenesis of many epithelial carcinomas, and emerging evidences suggest that delta NP63 is a promising drug target. However, the functions of delta NP63 in transitional cell carcinoma of bladder (TCCB) are poorly defined. In this study, a delta NP63 shRNA expression vector was transfected into TCCB cell line 5637 and cell cycling, cell proliferation and protein expression were assessed by flow cytometry and 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-dimethyl tetrazolium bromide (MTT) assay, and immunohistochemistry, respectively. The delta NP63 shRNA expression vector was also injected into 5637 cell xenograft tumors in nude mice, and tumor size was measured, tumor tissue morphology was assessed by immunohistopathology and transmission electron microscopy. In the in vitro study, delta NP63 shRNA transfection caused successful delta NP63 gene silencing and resulted in significant arrest of cell cycling and cellular proliferation (p<0.05) as well as cyclin D1 expression. In the nude mouse xenograft model, delta NP63 shRNA greatly inhibited tumor growth, induced tumor cell apoptosis (p<0.05) and resulted in cyclin D1 downregulation. Our data suggest that delta NP63 may play an oncogenic role in TCCB progression through promoting cell survival and proliferation. Intratumoral administration of delta NP63-specific shRNA suppressed tumor delta NP63 expression and cellular proliferation while promoted tumor cellular apoptosis, and therefore inhibited tumor growth and improved survival of xenograft-bearing mice, which was not accompanied by significant signs of systemic toxicity.


Subject(s)
Animals , Carcinoma, Transitional Cell/genetics , Cell Line, Tumor , Cell Proliferation , Cyclin D1/biosynthesis , Disease Progression , Female , Humans , Mice , Mice, Nude , Microscopy, Electron, Transmission , Models, Biological , Neoplasm Transplantation , Trans-Activators/biosynthesis , Tumor Suppressor Proteins/biosynthesis , Urinary Bladder Neoplasms/genetics
10.
El-Minia Medical Bulletin. 2005; 16 (2): 294-306
in English | IMEMR | ID: emr-70652

ABSTRACT

To date, molecular evidence studies for transitional cell carcinoma [TCC], using the microarray technology, are focusing on TCC of the urinary bladder and no studies have been performed on TCC of the upper urinary tract [UUT]. This study was conducted to monitor the gene expression profiles between transitional cell carcinoma of the upper urinary tract [TCC-UUT] and normal urothelium of UUT. cDNA microarrays were prepared by spotting PCR products of 14.551 human genes onto specially treated glass slides to analyze gene expression among 9 eases of TCC-UUT and 8 cases of normal urothelium in order to study the molecular basis of TCC-UUT development. Quantitative real time polymerase chain reaction [QRT-PCR] was performed for selected genes to validate the results of mieroarray hybridization. After supervised analysis of the microarray data, there was at least a 2.5-fold difference in the expression between TCC-UUT and normal urothelium in 55 genes. Significant up-regulation of 27 genes was associated with cases of TCC-UUT, including matrix degradation-related genes, as well as genes related to growth factors, immunology, cell-cycling and angiogenesis. Conversely, significant down-regulation of 28 genes was associated with eases of TCC-UUT including genes involved in epithelial cell dedifferentiation and keratinization, as well as genes related to cell adhesion and apoptosis. Such gene profiling studies can identify new molecular markers for early diagnosis and disease follow-up, it also allows the classification of tumors into subclasses assisting in disease diagnosis and prognosis, as well as in treatment selection


Subject(s)
Humans , Carcinoma, Transitional Cell/genetics , Cytogenetic Analysis , Oligonucleotide Array Sequence Analysis , Follow-Up Studies , Prognosis
11.
Int. braz. j. urol ; 30(4): 279-288, Jul.-Aug. 2004. ilus, tab
Article in English | LILACS | ID: lil-383742

ABSTRACT

PURPOSE: This study was conducted to examine: 1) whether the NAT2 genotypes are risk factors for bladder cancer, 2) to study possible association of tobacco usage with NAT2 genotype of these patients. MATERIALS AND METHODS: This case control study was undertaken over a period of 19 months and included 101 bladder cancer patients and 110 controls. The NAT2 genotypes were identified by PCR-RFLP method in peripheral blood DNA samples. Genotypes frequencies and the association of the genotypes among patients and controls group were assessed by chi2 test and Fisher exact test. RESULTS: The NAT2 fast acetylator genotype frequency of slow or fast acetylator genotypes was not significant in bladder cancer patients alone (OR = 1.18, 95 percent CI: 0.69 - 2.03, p value = 0.583) or combination with tobacco users (OR = 0.84, 95 percent CI: 0.328 - 2.125, p value = 0.813) when compared with controls. CONCLUSION: These data demonstrate that the NAT2 fast or slow acetylators genotype did not associated with the risk of developing bladder cancer in North Indian population when compared with controls.


Subject(s)
Adolescent , Aged , Humans , Middle Aged , Arylamine N-Acetyltransferase/genetics , Carcinoma, Transitional Cell/genetics , Polymorphism, Genetic , Urinary Bladder Neoplasms/genetics , Alleles , Case-Control Studies , DNA, Neoplasm/blood , DNA, Neoplasm/genetics , Gene Frequency , Genotype , India , Neoplasm Staging , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Risk Factors , Smoking
12.
São Paulo; s.n; 2004. 117 p. ilus, tab, graf.
Thesis in Portuguese | LILACS | ID: lil-397837

ABSTRACT

Este estudo incluiu 59 pacientes em que foram avaliadas as expressões das proteínas dos genes mdm-2, p53, e da família do gene bcl-2 por meio de método imunohistoquímico em carcinoma de células transicionais músculo-invasivo tratados com M-VAC, seguido do tratamento loco-regional. Este estudo procurou explorar a associação entre a expressão alterada destas proteínas com a sobrevida global. A expressão mínima ou ausente da proteína do gene p53 (p = 0.006) foi o único marcador que apresentou associação significativa, com taxas de sobrevida global mais favoráveis. /This study of 59 patients evaluated mdm-2, p53, and bcl-2 family gene protein expression by immunohistochemistry in muscle-invasive transitional cell carcinoma of urinary bladder treated with M-VAC, followed by locoregional treatment. This study explored the relationship between altered expression and long-term survival in this patient population. Absence or minimal p53 gene protein expression (p = 0.006) was the only molecular marker that statistically correlated with prolonged survival. However, the cooperative effects of mdm-2, p53, and bcl-2 genes represented a more robust prognostic model to delineate overall survival (p = 0.01) compared to isolated gene proteins...


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Carcinoma, Transitional Cell/genetics , Urinary Bladder Neoplasms/genetics , Tumor Suppressor Protein p53 , Immunohistochemistry , Prognosis
13.
Rev. argent. urol. (1990) ; 66(2): 61-69, abr.-jun. 2001. ilus
Article in Spanish | LILACS | ID: lil-307014

ABSTRACT

Objetivo: Tratar de establecxer una revisión bibliográfica actualizada de los conocimientos sobre la biología y los factores pronósticos en el carcinoma transicional de vejiga localmenmte avanzado. Material y métodos : se revisó bibliografía obtenida a través de Medline, internet, libros de texto, revistas, etc sobre el tema de estudio. Resultados: La necesidad de predecir la conducta de los tumores infiltrativos vesicales ha llevado


Subject(s)
Humans , Carcinoma, Transitional Cell/physiopathology , Carcinoma, Transitional Cell/genetics , Biomarkers, Tumor , Urinary Bladder Neoplasms , Prognosis
14.
Yonsei Medical Journal ; : 371-379, 1996.
Article in English | WPRIM | ID: wpr-213092

ABSTRACT

To investigate the incidence of the H-ras gene activation in bladder tumor and the feasibility of using urinary washout samples for screening, a series of 33 human bladder tumors and their preoperatively collected urinary washout samples were screened using a mutant specific PCR-RFLP (polymerase chain-restriction fragment length polymorphism) to detect a point mutation of the H-ras gene. Five tumors were found to harbor H-ras mutations where two tumors had a glycine to valine (G-->T) change in codon 12 and three tumors had a glutamine to lysine (C-->A) change in codon 61, respectively. Moreover, we could also detect the same point mutations of the H-ras gene in corresponding urine washout samples. The incidence of H-ras mutation in Korean bladder cancer was estimated at approximately 15.2%. In conclusion, a mutant specific PCR-RFLP method for the detection of H-ras gene mutation is useful for screening or postoperative follow-up of bladder tumor due to its simplicity and high specificity even in urinary samples.


Subject(s)
Base Sequence , Urinary Bladder Neoplasms/genetics , Carcinoma, Transitional Cell/genetics , Codon , Gene Expression Regulation , Genes, ras , Humans , Molecular Sequence Data , Point Mutation , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length
15.
Article in English | WPRIM | ID: wpr-212620

ABSTRACT

The objective of this study was to characterize the alterations of 9p21 and TP53 in Korean transitional bladder cancer and to assess the relationship between the histopathologic parameter and the alteration of these genes. Allele loss in 29 surgically resected transitional cell carcinoma was examined by using the multiplex PCR with 7 and 1 microsatellite markers for 9p21 and TP53, respectively. Twenty-one (72%) demonstrated allele loss at 9p21 and/or TP53. Deletion at the 9p21 region was detected in 17(61%) of 28 informative cases at one or more loci, and LOH at TP53 was found in 12(55%) of 22 informative cases. Of 7 microsatellite markers for 9p21, allele loss occurred the most frequently at locus D9S162(69%) and D9S104(69%). Additionally, hemizygous deletion was slightly more common than homozygous deletion. Deletion at 9p21 and TP53 was not related with increased grade. These results suggest that the alteration of 9p21 may be an early event in the development of Korean bladder cancer, while p53 gene may be involved in early event of some bladder cancers as well as in their late events.


Subject(s)
Adult , Aged , Urinary Bladder Neoplasms/genetics , Carcinoma, Transitional Cell/genetics , Chromosome Deletion , Chromosomes, Human, Pair 9 , Female , Genes, p53 , Humans , Male , Middle Aged
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